Tubulin polymerization-promoting protein (TPPP)

Tubulin polymerization-promoting protein (TPPP), also called TPPP1 or p25alpha, is a brain-enriched, intrinsically disordered microtubule-associated protein that promotes assembly, bundling, and stabilization of microtubules and increases tubulin acetylation by inhibiting tubulin deacetylases such as HDAC6[1][2][3][5]. TPPP is highly expressed in oligodendrocytes, where it facilitates myelination and process extension, and its dysfunction or aggregation, especially in association with α-synuclein, is implicated in the pathogenesis of several neurodegenerative diseases including Parkinson’s disease and multiple system atrophy[1][2][3]. TPPP acts as a "moonlighting" protein, with roles in both physiological cytoskeletal regulation and pathological protein aggregation[1][2]. It is involved in microtubule cytoskeleton organization, negative regulation of tubulin deacetylation, positive regulation of protein polymerization, and cell cycle regulation[2][3]. TPPP has been genetically linked as a modifier of cystic fibrosis lung disease severity and contributes to inflammatory responses when dysregulated[5]. There are currently no approved drugs targeting TPPP directly, but it is considered an emerging target in neurodegenerative disease research, especially regarding pathological protein aggregation[1][2][5].

Other names

TPPP1p25alphap25TPPP/p2525 kDa brain-specific proteinp24brain specific protein p25 alphaglycogen synthase kinase 3 (GSK3) inhibitor p24p25-alpha

No unique small molecule mechanism is established in drug literature; candidate therapeutic strategies include inhibitors of TPPP/α-synuclein interaction and modulating HDAC6-mediated tubulin deacetylation